Invited Speaker Abstract 2018 Hunter Cell Biology Meeting

Targeting BCL-2 Pro-Survival Proteins for Cancer Therapy (#30)

Gemma Kelly

Evasion from apoptosis is critical for the development and expansion of malignant tumours. This was first shown for lymphomas that were elicited by deregulated expression of the cell cycle regulator c-MYC, which is abnormally over-expressed in ~70% of human cancers. Identifying the factors critical for the sustained growth of established MYC-driven lymphomas remains an important objective. In earlier work using Eµ-Myc mouse lymphomas and human Burkitt lymphoma (BL) we have demonstrated that tumour growth is dependent on the expression of the BCL-2 pro-survival family member, MCL-1 (Kelly et al G&D 2014). A new class of drugs termed BH3-mimetic drugs has been developed that can bind to BCL-2 pro-survival family proteins and induce death of cancer cells. We have assessed the efficacy and potential toxicities of a new BH3-mimetic drug targeting MCL-1. Our results suggest that targeting of MCL-1 could be an attractive therapeutic strategy for the treatment of MYC-driven lymphomas.